Clinical trajectory of KRAS G12C-mutated advanced non-small cell lung cancer: a single-center cohort study in Japan

KRAS gene mutations occur in approximately 32% of lung adenocarcinomas in Western countries and 9.7% in Japan, with G12C being the most common. KRAS-mutated non-small cell lung cancer (NSCLC) typically has a poor prognosis regardless of mutation subtype. In Japan, the KRAS G12C inhibitor sotorasib became available in January 2022 for second-line and later use, and clinical benefit is expected. However, the proportion of patients proceeding to second-line treatment following first-line disease progression remains low.

Medical records of patients diagnosed with KRAS-mutated NSCLC between July 2019 and January 2024 at Kansai Medical University Hospital were retrospectively reviewed. Patients with confirmed KRAS G12C mutations were evaluated for clinical trajectory, transition to second-line therapy, weight change, treatment effectiveness, overall survival (OS), and progression-free survival (PFS).

Among 79 patients with KRAS-mutated NSCLC, the G12C subtype was most frequent, found in 23 patiens (30%). Sixteen patients received treatment, with median PFS and OS of 7.5 months (95% confidence interval [CI]: 3.7-not applicable [NA]) and 14.9 months (95% CI: 6.7-NA), respectively. Although disease progression occurred in 11/16 patients (68%), only three (27%) transitioned to sotorasib. Of the patients treated with first-line therapy, eight had evaluable longitudinal weight data. The average rate of weight loss from the CT response evaluation at the time point preceding PD to the time of PD determination was 7.5% (range: 1.5-13.9).

In KRAS G12C-mutated NSCLC, limited second-line therapy uptake persists. Weight monitoring may enable earlier detection of progression and improve access to second-line treatment.